Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 55 Records) |
Query Trace: Flint M [original query] |
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Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel
Lester SN , Stumpf M , Freeman BD , Mills L , Schiffer J , Semenova V , Jia T , Desai R , Browning P , Alston B , Ategbole M , Bolcen S , Chen A , David E , Manitis P , Tatum H , Qin Y , Zellner B , Drobeniuc J , Tejada-Strop A , Chatterjee P , Shrivastava-Ranjan P , Jenks MH , McMullan LK , Flint M , Spiropoulou CF , Niemeyer GP , Werner BJ , Bean CJ , Johnson JA , Hoffmaster AR , Satheshkumar PS , Schuh AJ , Owen SM , Thornburg NJ . Access Microbiol 2024 6 (2) Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients' sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4-96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies. |
Development of reverse genetic tools to study Chapare and Machupo viruses
Jain S , Shrivastava-Ranjan P , Flint M , Montgomery JM , Spiropoulou CF , Albariño CG . Virology 2023 588 109888 Arenaviruses are highly pathogenic viruses that pose a serious public health threat. Chapare virus (CHAV) and Machupo virus (MACV), two New World arenaviruses, cause hemorrhagic fevers with case fatality rates of up to 45%. Research on therapeutic drug targets and vaccines for these viruses is limited because biosafety level 4 containment is required for handling them. In this study, we developed reverse genetics systems, including minigenomes and recombinant viruses, that will facilitate the study of these pathogens. The minigenome system is based on the S segment of CHAV or MACV genomes expressing the fluorescent reporter gene ZsGreen (ZsG). We also generated recombinant CHAV and MACV with and without the ZsG reporter gene. As a proof-of-concept study, we used both minigenomes and recombinant viruses to test the inhibitory effects of previously reported antiviral compounds. The new reverse genetics system described here will facilitate future therapeutic studies for these two life-threatening arenaviruses. |
Broad-spectrum in vitro antiviral activity of ODBG-P-RVn: an orally-available, lipid-modified monophosphate prodrug of remdesivir parent nucleoside (GS-441524) (preprint)
Lo MK , Shrivastava-Ranjan P , Chatterjee P , Flint M , Beadle JR , Valiaeva N , Schooley RT , Hostetler KY , Montgomery JM , Spiropoulou C . bioRxiv 2021 The intravenous administration of remdesivir for COVID-19 confines its utility to hospitalized patients. We evaluated the broad-spectrum antiviral activity of ODBG-P-RVn, an orally available, lipid-modified monophosphate prodrug of the remdesivir parent nucleoside (GS-441524) against viruses that cause diseases of human public health concern, including SARS-CoV-2. ODBG-P-RVn showed 20-fold greater antiviral activity than GS-441524 and had near-equivalent activity to remdesivir in primary-like human small airway epithelial cells. Our results warrant investigation of ODBG-P-RVn efficacy in vivo. |
Development of a novel minigenome and recombinant VSV expressing Seoul hantavirus glycoprotein-based assays to identify anti-hantavirus therapeutics
Shrivastava-Ranjan P , Jain S , Chatterjee P , Montgomery JM , Flint M , Albariño C , Spiropoulou CF . Antiviral Res 2023 214 105619 Seoul virus (SEOV) is an emerging global health threat that can cause hemorrhagic fever with renal syndrome (HFRS), which results in case fatality rates of ∼2%. There are no approved treatments for SEOV infections. We developed a cell-based assay system to identify potential antiviral compounds for SEOV and generated additional assays to characterize the mode of action of any promising antivirals. To test if candidate antivirals targeted SEOV glycoprotein-mediated entry, we developed a recombinant reporter vesicular stomatitis virus expressing SEOV glycoproteins. To facilitate the identification of candidate antiviral compounds targeting viral transcription/replication, we successfully generated the first reported minigenome system for SEOV. This SEOV minigenome (SEOV-MG) screening assay will also serve as a prototype assay for discovery of small molecules inhibiting replication of other hantaviruses, including Andes and Sin Nombre viruses. Ours is a proof-of-concept study in which we tested several compounds previously reported to have activity against other negative-strand RNA viruses using our newly developed hantavirus antiviral screening systems. These systems can be used under lower biocontainment conditions than those needed for infectious viruses, and identified several compounds with robust anti-SEOV activity. Our findings have important implications for the development of anti-hantavirus therapeutics. |
One Health Investigation of SARS-CoV-2 in People and Animals on Multiple Mink Farms in Utah.
Cossaboom CM , Wendling NM , Lewis NM , Rettler H , Harvey RR , Amman BR , Towner JS , Spengler JR , Erickson R , Burnett C , Young EL , Oakeson K , Carpenter A , Kainulainen MH , Chatterjee P , Flint M , Uehara A , Li Y , Zhang J , Kelleher A , Lynch B , Retchless AC , Tong S , Ahmad A , Bunkley P , Godino C , Herzegh O , Drobeniuc J , Rooney J , Taylor D , Barton Behravesh C . Viruses 2022 15 (1) From July-November 2020, mink (Neogale vison) on 12 Utah farms experienced an increase in mortality rates due to confirmed SARS-CoV-2 infection. We conducted epidemiologic investigations on six farms to identify the source of virus introduction, track cross-species transmission, and assess viral evolution. Interviews were conducted and specimens were collected from persons living or working on participating farms and from multiple animal species. Swabs and sera were tested by SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) and serological assays, respectively. Whole genome sequencing was attempted for specimens with cycle threshold values <30. Evidence of SARS-CoV-2 infection was detected by rRT-PCR or serology in ≥1 person, farmed mink, dog, and/or feral cat on each farm. Sequence analysis showed high similarity between mink and human sequences on corresponding farms. On farms sampled at multiple time points, mink tested rRT-PCR positive up to 16 weeks post-onset of increased mortality. Workers likely introduced SARS-CoV-2 to mink, and mink transmitted SARS-CoV-2 to other animal species; mink-to-human transmission was not identified. Our findings provide critical evidence to support interventions to prevent and manage SARS-CoV-2 in people and animals on mink farms and emphasizes the importance of a One Health approach to address emerging zoonoses. |
Engagement in the MI-SIGHT Glaucoma Screening Program: Comparing the effect of clinic versus community-based recruitment strategies
Elam AR , Mobolaji I , Flaharty K , Niziol LM , Woodward MA , Zhang J , Musch DC , Johnson L , Kershaw M , Bicket A , Saaddine J , John D , Newman-Casey PA . Ophthalmol Glaucoma 2022 PURPOSE: To determine the effectiveness of adding community-based recruitment to clinic-based recruitment to engage participants in a glaucoma detection program. DESIGN: Prospective cohort study. SUBJECTS: Anyone ≥ 18 years of age who do not meet exclusion criteria METHODS: The Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine (MI-SIGHT) Program tests a novel way of improving glaucoma detection in communities with populations at high risk for disease, including people who identify as Black and Hispanic and those living with low socio-economic status. The MI-SIGHT program is conducted in a free clinic (Ypsilanti, MI) and in a federally qualified health center (FQHC; Flint, MI). Community-engagement methods were used to identify outreach strategies to enhance recruitment. Participants were asked "How did you hear about the MI-SIGHT program?" and responses were summarized overall and by clinic and compared between clinic-based and community-based recruitment strategies. MAIN OUTCOME MEASURES: Proportion recruited by location, within or outside of the clinic. RESULTS: 647 participants were recruited in the first eleven months of the study, 356 (55.0%) at the free clinic over 11 months and 291 (45.0%) at the FQHC over 6 months. Participants were on average 54.4 years old (SD=14.2), 60.9% female, 45.6% Black, 37.8% White, 9.6% Hispanic, and 10.9% had < high school education. Participants reported hearing about the MI-SIGHT program from a clinic phone call (n=168, 26.1%), a friend (n=112, 17.4%), non-medical clinic staff (n=100, 15.5%), a clinic doctor (n=77, 11.9%), an in-clinic brochure or flyer (n=51, 7.9%), a community flyer (n=44, 6.8%), the clinic website or social media (n=28, 4.3%), or an "other" source (n=65, 10.1%). Recruiting from the community outside the medical clinics increased participation by 265% at the free clinic and 46% at the FQHC. CONCLUSIONS: The Community Advisory Board recommendation to use community-based recruitment strategies in addition to clinic-based strategies for recruitment resulted in increased program participation. |
Broad-Spectrum In Vitro Antiviral Activity of ODBG-P-RVn: An Orally-Available, Lipid-Modified Monophosphate Prodrug of Remdesivir Parent Nucleoside (GS-441524).
Lo MK , Shrivastava-Ranjan P , Chatterjee P , Flint M , Beadle JR , Valiaeva N , Murphy J , Schooley RT , Hostetler KY , Montgomery JM , Spiropoulou CF . Microbiol Spectr 2021 9 (3) e0153721 The necessity for intravenous administration of remdesivir confines its utility for treatment of coronavirus disease 2019 (COVID-19) to hospitalized patients. We evaluated the broad-spectrum antiviral activity of ODBG-P-RVn, an orally available, lipid-modified monophosphate prodrug of the remdesivir parent nucleoside (GS-441524), against viruses that cause diseases of human public health concern, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ODBG-P-RVn showed 20-fold greater antiviral activity than GS-441524 and had activity nearly equivalent to that of remdesivir in primary-like human small airway epithelial cells. Our results warrant in vivo efficacy evaluation of ODBG-P-RVn. IMPORTANCE While remdesivir remains one of the few drugs approved by the FDA to treat coronavirus disease 2019 (COVID-19), its intravenous route of administration limits its use to hospital settings. Optimizing the stability and absorption of remdesivir may lead to a more accessible and clinically potent therapeutic. Here, we describe an orally available lipid-modified version of remdesivir with activity nearly equivalent to that of remdesivir against emerging viruses that cause significant disease, including Ebola and Nipah viruses. Our work highlights the importance of such modifications to optimize drug delivery to relevant and appropriate human tissues that are most affected by such diseases. |
Screening and Identification of Lujo Virus Inhibitors Using a Recombinant Reporter Virus Platform.
Welch SR , Spengler JR , Genzer SC , Chatterjee P , Flint M , Bergeron É , Montgomery JM , Nichol ST , Albariño CG , Spiropoulou CF . Viruses 2021 13 (7) Lujo virus (LUJV), a highly pathogenic arenavirus, was first identified in 2008 in Zambia. To aid the identification of effective therapeutics for LUJV, we developed a recombinant reporter virus system, confirming reporter LUJV comparability with wild-type virus and its utility in high-throughput antiviral screening assays. Using this system, we evaluated compounds with known and unknown efficacy against related arenaviruses, with the aim of identifying LUJV-specific and potential new pan-arenavirus antivirals. We identified six compounds demonstrating robust anti-LUJV activity, including several compounds with previously reported activity against other arenaviruses. These data provide critical evidence for developing broad-spectrum antivirals against high-consequence arenaviruses. |
High-throughput quantitation of SARS-CoV-2 antibodies in a single-dilution homogeneous assay.
Kainulainen MH , Bergeron E , Chatterjee P , Chapman AP , Lee J , Chida A , Tang X , Wharton RE , Mercer KB , Petway M , Jenks HM , Flietstra TD , Schuh AJ , Satheshkumar PS , Chaitram JM , Owen SM , McMullan LK , Flint M , Finn MG , Goldstein JM , Montgomery JM , Spiropoulou CF . Sci Rep 2021 11 (1) 12330 SARS-CoV-2 emerged in late 2019 and has since spread around the world, causing a pandemic of the respiratory disease COVID-19. Detecting antibodies against the virus is an essential tool for tracking infections and developing vaccines. Such tests, primarily utilizing the enzyme-linked immunosorbent assay (ELISA) principle, can be either qualitative (reporting positive/negative results) or quantitative (reporting a value representing the quantity of specific antibodies). Quantitation is vital for determining stability or decline of antibody titers in convalescence, efficacy of different vaccination regimens, and detection of asymptomatic infections. Quantitation typically requires two-step ELISA testing, in which samples are first screened in a qualitative assay and positive samples are subsequently analyzed as a dilution series. To overcome the throughput limitations of this approach, we developed a simpler and faster system that is highly automatable and achieves quantitation in a single-dilution screening format with sensitivity and specificity comparable to those of ELISA. |
Design, synthesis and biological evaluation of 2-substituted-6-[(4-substituted-1-piperidyl)methyl]-1H-benzimidazoles as inhibitors of ebola virus infection
Bessières M , Plebanek E , Chatterjee P , Shrivastava-Ranjan P , Flint M , Spiropoulou CF , Warszycki D , Bojarski AJ , Roy V , Agrofoglio LA . Eur J Med Chem 2021 214 113211 Novel 2-substituted-6-[(4-substituted-1-piperidyl)methyl]-1H-benzimidazoles were designed and synthesized as Ebola virus inhibitors. The proposed structures of the new prepared benzimidazole-piperidine hybrids were confirmed based on their spectral data and CHN analyses. The target compounds were screened in vitro for their anti-Ebola activity. Among tested molecules, compounds 26a (EC(50=)0.93 μM, SI = 10) and 25a (EC(50=)0.64 μM, SI = 20) were as potent as and more selective than Toremifene reference drug (EC(50) = 0.38 μM, SI = 7) against cell line. Data suggests that the mechanism by which 25a and 26a block EBOV infection is through the inhibition of viral entry at the level of NPC1. Furthermore, a docking study revealed that several of the NPC1 amino acids that participate in binding to GP are involved in the binding of the most active compounds 25a and 26a. Finally, in silico ADME prediction indicates that 26a is an idealy drug-like candidate. Our results could enable the development of small molecule drug capable of inhibiting Ebola virus, especially at the viral entry step. |
Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine (MI-SIGHT): Baseline methodology for implementing and assessing a community-based program
Newman-Casey PA , Musch DC , Niziol LM , Elam AR , Zhang J , Moroi SE , Johnson L , Kershaw M , Saadine J , Winter S , Woodward MA . J Glaucoma 2021 30 (5) 380-387 PRECIS: The Michigan Screening and Intervention for Glaucoma and eye Health through Telemedicine Program leverages community engaged research, telemedicine and health coaching to overcome key logistical and psychosocial barriers to improved glaucoma screening in underserved communities. PURPOSE: To describe the methodology of the implementation and evaluation of the Michigan Screening and Intervention for Glaucoma and eye Health through Telemedicine (MI-SIGHT) Program. METHODS: The MI-SIGHT Program utilizes community engagement, telemedicine and health coaching to overcome key logistical and psychosocial barriers to glaucoma identification and care among underserved populations. The MI-SIGHT Program will be evaluated in two community clinics: Hamilton Community Health Network, a federally qualified health center in Flint, MI, and the Hope Clinic, a free clinic in Ypsilanti, MI. A Community Advisory Board including the research team and health care providers, administrators and patients from both clinics will guide program implementation. An ophthalmic technician at the community clinics will conduct screening tests for glaucoma and eye disease. The data will be transmitted via electronic health record to be reviewed by an ophthalmologist who will make recommendations for follow-up care. The ophthalmic technician will conduct a return visit to fit low-or no-cost glasses, help arrange follow-up with an ophthalmologist and provide education. Those diagnosed with glaucoma or suspected glaucoma will be randomized to standard education or personalized glaucoma education and coaching. Costs will be assessed. RESULTS: We hypothesize that the MI-SIGHT program will detect a higher prevalence rate of glaucoma than that found in the general population, improve upon presenting visual acuity, enhance vision-related quality of life and demonstrate that personalized glaucoma education and coaching improve adherence to follow-up care. CONCLUSION: The MI-SIGHT Program may serve as a model for glaucoma screening and care in high-risk communities. |
Hantavirus infection is inhibited by griffithsin in cell culture
Shrivastava-Ranjan P , Lo MK , Chatterjee P , Flint M , Nichol ST , Montgomery JM , O'Keefe BR , Spiropoulou CF . Front Cell Infect Microbiol 2020 10 561502 Andes virus (ANDV) and Sin Nombre virus (SNV), highly pathogenic hantaviruses, cause hantavirus pulmonary syndrome in the Americas. Currently no therapeutics are approved for use against these infections. Griffithsin (GRFT) is a high-mannose oligosaccharide-binding lectin currently being evaluated in phase I clinical trials as a topical microbicide for the prevention of human immunodeficiency virus (HIV-1) infection (ClinicalTrials.gov Identifiers: NCT04032717, NCT02875119) and has shown broad-spectrum in vivo activity against other viruses, including severe acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, and Nipah virus. In this study, we evaluated the in vitro antiviral activity of GRFT and its synthetic trimeric tandemer 3mGRFT against ANDV and SNV. Our results demonstrate that GRFT is a potent inhibitor of ANDV infection. GRFT inhibited entry of pseudo-particles typed with ANDV envelope glycoprotein into host cells, suggesting that it inhibits viral envelope protein function during entry. 3mGRFT is more potent than GRFT against ANDV and SNV infection. Our results warrant the testing of GRFT and 3mGRFT against ANDV infection in animal models. |
Remdesivir targets a structurally analogous region of the Ebola virus and SARS-CoV-2 polymerases.
Lo MK , Albariño CG , Perry JK , Chang S , Tchesnokov EP , Guerrero L , Chakrabarti A , Shrivastava-Ranjan P , Chatterjee P , McMullan LK , Martin R , Jordan R , Götte M , Montgomery JM , Nichol ST , Flint M , Porter D , Spiropoulou CF . Proc Natl Acad Sci U S A 2020 117 (43) 26946-26954 Remdesivir is a broad-spectrum antiviral nucleotide prodrug that has been clinically evaluated in Ebola virus patients and recently received emergency use authorization (EUA) for treatment of COVID-19. With approvals from the Federal Select Agent Program and the Centers for Disease Control and Prevention's Institutional Biosecurity Board, we characterized the resistance profile of remdesivir by serially passaging Ebola virus under remdesivir selection; we generated lineages with low-level reduced susceptibility to remdesivir after 35 passages. We found that a single amino acid substitution, F548S, in the Ebola virus polymerase conferred low-level reduced susceptibility to remdesivir. The F548 residue is highly conserved in filoviruses but should be subject to specific surveillance among novel filoviruses, in newly emerging variants in ongoing outbreaks, and also in Ebola virus patients undergoing remdesivir therapy. Homology modeling suggests that the Ebola virus polymerase F548 residue lies in the F-motif of the polymerase active site, a region that was previously identified as susceptible to resistance mutations in coronaviruses. Our data suggest that molecular surveillance of this region of the polymerase in remdesivir-treated COVID-19 patients is also warranted. |
Shigella sonnei Outbreak Investigation During a Municipal Water Crisis-Genesee and Saginaw Counties, Michigan, 2016.
McClung RP , Karwowski M , Castillo C , McFadden J , Collier S , Collins J , Soehnlen M , Dietrich S , Trees E , Wilt G , Harrington C , Miller A , Adam E , Reses H , Cope J , Fullerton K , Hill V , Yoder J . Am J Public Health 2020 110 (6) e1-e8 Objectives. To investigate a shigellosis outbreak in Genesee County, Michigan (including the City of Flint), and Saginaw County, Michigan, in 2016 and address community concerns about the role of the Flint water system.Methods. We met frequently with community members to understand concerns and develop the investigation. We surveyed households affected by the outbreak, analyzed Shigella isolate data, examined the geospatial distribution of cases, and reviewed available water quality data.Results. We surveyed 83 households containing 158 cases; median age was 10 years. Index case-patients from 55 of 83 households (66%) reported contact with a person outside their household who wore diapers or who had diarrhea in the week before becoming ill; results were similar regardless of household drinking water source. Genomic diversity was not consistent with a point source. In Flint, no space-time clustering was identified, and average free chlorine residual values remained above recommended levels throughout the outbreak period.Conclusions. The outbreak was most likely caused by person-to-person contact and not by the Flint water system. Consistent community engagement was essential to the design and implementation of the investigation. (Am J Public Health. Published online ahead of print April 16, 2020: e1-e8. doi:10.2105/AJPH.2020.305577). |
Potent in vitro activity of beta-D-4'-chloromethyl-2'-deoxy-2'-fluorocytidine against Nipah virus
Lo MK , Amblard F , Flint M , Chatterjee P , Kasthuri M , Li C , Russell O , Verma K , Bassit L , Schinazi RF , Nichol ST , Spiropoulou CF . Antiviral Res 2020 175 104712 Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that continues to cause outbreaks in humans characterized by high mortality and significant clinical sequelae in survivors. Currently, no therapeutics are approved for use in humans against NiV infection. Here, we report that 4'-chloromethyl-2'-deoxy-2'-fluorocytidine (ALS-8112) inhibits NiV. ALS-8112 is the parent nucleoside of lumicitabine, which has been evaluated in phase I and II clinical trials to treat pediatric and adult respiratory syncytial virus infection. In this study, we tested ALS-8112 against NiV and other major human respiratory pneumo- and paramyxoviruses in 2 human lung epithelial cell lines, and demonstrated the ability of ALS-8112 to reduce infectious wild-type NiV yield by over 6 orders of magnitude with no apparent cytotoxicity. However, further cytotoxicity testing in primary cells and bone marrow progenitor cells indicated cytotoxicity at higher concentrations of ALS-8112. Our results warrant the evaluation of lumicitabine against NiV infection in relevant animal models. |
Lessons from the first 6 years of an intervention-based field epidemiology training programme in Papua New Guinea, 2013-2018
Ropa B , Flint J , O'Reilly M , Pavlin BI , Dagina R , Peni B , Bauri M , Pukienei A , Merritt T , Terrell-Perica S , Yamba A , Prybylski D , Collins J , Durrheim DN , Henderson A , Bieb S . BMJ Glob Health 2019 4 (6) e001969 Papua New Guinea (PNG) faces a critical shortage of human resources to address pressing public health challenges arising from an increasing burden of communicable and non-communicable diseases. PNG is an independent State in the Pacific and home to 8.2 million people. Resource and infrastructure constraints due to the country's challenging geography have made it difficult and expensive to deliver health services and implement health programmes. The National Department of Health and its partners developed a field epidemiology training programme of Papua New Guinea (FETPNG) to strengthen the country's public health workforce. The training programme covers field epidemiology competencies and includes the design, implementation and evaluation of evidence-based interventions by Fellows. From 2013 to 2018, FETPNG graduated 81 field epidemiologists. Most FETPNG graduates (84%) were from provincial or district health departments or organisations. Many of their intervention projects resulted in successful public health outcomes with tangible local impacts. Health challenges addressed included reducing the burden of multi-drug resistant-tuberculosis (TB), increasing immunisation coverage, screening and treating HIV/TB patients, and improving reproductive health outcomes. FETPNG Fellows and graduates have also evaluated disease surveillance systems and investigated disease outbreaks. Early and unwavering national ownership of FETPNG created a sustainable programme fitting the needs of this low-resource country. A focus on designing and implementing effective public health interventions not only provides useful skills to Fellows but also contributes to real-time, tangible and meaningful improvements in the health of the population. The graduates of FETPNG now provide a critical mass of public health practitioners across the country. Their skills in responding to outbreaks and public health emergencies, in collecting, analysing and interpreting data, and in designing, implementing and evaluating public health interventions continues to advance public health in PNG. |
A fresh look at stress and resilience in communities affected by environmental contamination
Gerhardstein B , Tucker PG , Rayman J , Reh CM . J Environ Health 2019 82 (4) 36-38 From toxic waste in Love Canal, New York, to lead in Flint, Michigan, environmental contamination can cause chronically elevated psychosocial stress (see sidebar) in individuals and across families and communities (Cuthbertson, Newkirk, Loveridge, & Skidmore, 2016; Edelstein, 2004; Levine, 1983). Stress is a normal reaction to environmental contamination, not a mental health disorder. Still, stress can affect people’s health and quality of life. | | Environmental contamination can cause psychosocial stress among affected community members for many reasons, including: | | Uncertainty: At the individual level, people might not know whether, at what level or for how long, they were exposed. Moreover, scientists and physicians might be uncertain about the possible health effects of exposure. | Health and safety concerns: At a family level, parents might worry about their children’s health. They might feel their home is not a safe place anymore. | Social conflict: At the community level, there can be discord between community members who have differing beliefs about the seriousness of the threat. |
Probing the effects of pyrimidine functional group switches on acyclic fleximer analogues for antiviral activity
Yates MK , Chatterjee P , Flint M , Arefeayne Y , Makuc D , Plavec J , Spiropoulou CF , Seley-Radtke KL . Molecules 2019 24 (17) Due to their ability to inhibit viral DNA or RNA replication, nucleoside analogues have been used for decades as potent antiviral therapeutics. However, one of the major limitations of nucleoside analogues is the development of antiviral resistance. In that regard, flexible nucleoside analogues known as "fleximers" have garnered attention over the years due to their ability to survey different amino acids in enzyme binding sites, thus overcoming the potential development of antiviral resistance. Acyclic fleximers have previously demonstrated antiviral activity against numerous viruses including Middle East Respiratory Syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and, most recently, flaviviruses such as Dengue (DENV) and Yellow Fever Virus (YFV). Due to these interesting results, a Structure Activity Relationship (SAR) study was pursued in order to analyze the effect of the pyrimidine functional group and acyl protecting group on antiviral activity, cytotoxicity, and conformation. The results of those studies are presented herein. |
Characterisation of infectious Ebola virus from the ongoing outbreak to guide response activities in the Democratic Republic of the Congo: a phylogenetic and in vitro analysis.
McMullan LK , Flint M , Chakrabarti A , Guerrero L , Lo MK , Porter D , Nichol ST , Spiropoulou CF , Albarino C . Lancet Infect Dis 2019 19 (9) 1023-1032 BACKGROUND: The ongoing Ebola virus outbreak in the Ituri and North Kivu Provinces of the Democratic Republic of the Congo, which began in July, 2018, is the second largest ever recorded. Despite civil unrest, outbreak control measures and the administration of experimental therapies and a vaccine have been initiated. The aim of this study was to test the efficacy of candidate therapies and diagnostic tests with the outbreak strain Ituri Ebola virus. Lacking a virus isolate from this outbreak, a recombinant Ituri Ebola virus was compared with a similarly engineered Makona virus from the 2013-16 outbreak. METHODS: Using Ebola virus sequences provided by organisations in DR Congo and a reverse genetics system, we generated an authentic Ebola virus from the ongoing outbreak in Ituri and North Kivu provinces. To relate this virus to other Ebola viruses in DR Congo, we did a phylogenetic analysis of representative complete Ebola virus genome sequences from previous outbreaks. We evaluated experimental therapies being tested in clinical trials in DR Congo, including remdesivir and ZMapp monoclonal antibodies, for their ability to inhibit the growth of infectious Ituri Ebola virus in cell culture. We also tested diagnostic assays for detection of the Ituri Ebola virus sequence. FINDINGS: The phylogenetic analysis of whole-genome sequences from each Ebola virus outbreak suggests there are at least two Ebola virus strains in DR Congo, which have independently crossed into the human population. The Ituri Ebola strain initially grew slower than the Makona strain, yet reached similar mean yields of 3 x 10(7) 50% tissue culture infectious dose by 72 h infection in Huh-7 cells. Ituri Ebola virus was similar to Makona in its susceptibility to inhibition by remdesivir and to neutralisation by monoclonal antibodies from ZMapp and other monoclonal antibodies. Remdesivir inhibited Ituri Ebola virus at a 50% effective concentration (EC50) of 12nM (with a selectivity index of 303) and Makona Ebola virus at 13nM (with a selectivity index of 279). The Zmapp monoclonal antibodies 2G4 and 4G7 neutralised Ituri Ebola virus with a mean EC50 of 0.24 mug/mL and 0.48 mug/mL, and Makona Ebola virus with a mean EC50 of 0.45 mug/mL and 0.2 mug/mL. The Xpert Ebola and US Centers for Disease Control and Prevention real-time RT-qPCR diagnostic assays detected Ituri and Makona Ebola virus sequences with similar sensitivities and efficiencies, despite primer site binding mismatches in the Ituri Ebola virus. INTERPRETATION: Our findings provide a rationale for the continued testing of investigational therapies, confirm the effectiveness of the diagnostic assays used in the region, and establish a paradigm for the use of reverse genetics to inform response activities in an outbreak. FUNDING: US Centers for Disease Control and Prevention. |
Childhood lead poisoning: A perpetual environmental justice issue
Whitehead LS , Buchanan SD . J Public Health Manag Pract 2019 25 S115-s120 As the amount of lead in the environment has significantly decreased with the removal of lead in gasoline and paint, the United States has made great strides in preventing lead poisoning or reducing levels of lead in young children's blood. Even so, lead exposure is not equal for all children-low-income and minority children continue to bear a disproportionate burden of exposure primarily through contact with deteriorating lead-based paint from older housing and potentially through drinking contaminated water resulting from failing leaded pipes, as evidenced by the recent events in Flint, Michigan. These facts suggest that childhood lead poisoning is an environmental justice issue worthy of public health consideration and action; "environmental justice" is focused on identifying and addressing disproportionately high and adverse effects of environmental hazards on low-income and minority communities. The question remains, however, as to whether addressing the quality-of-life "risk" factors associated with lead poisoning might eventually lead to reduction in exposure, as well as potentially resulting in adverse health effects. Utilizing an environmental justice framework and examining this issue through a multidimensional environmental justice lens, we contemplated the quality-of-life factors that may essentially predispose minority children and their families to lead poisoning. Specifically, we examined American Community Survey data (2012-2016) focused on comparing race/ethnicity with other sociodemographic variables known to be associated with risks for childhood lead poisoning. The results provide thought-provoking context for making progress toward eliminating lead poisoning as a major environmental justice concern. |
The Flint Water Crisis: A coordinated public health emergency response and recovery initiative
Ruckart PZ , Ettinger AS , Hanna-Attisha M , Jones N , Davis SI , Breysse PN . J Public Health Manag Pract 2019 25 S84-s90 CONTEXT: The City of Flint was already distressed because of decades of financial decline when an estimated 140 000 individuals were exposed to lead and other contaminants in drinking water. In April 2014, Flint's drinking water source was changed from Great Lakes' Lake Huron (which was provided by the Detroit Water and Sewerage Department) to the Flint River without necessary corrosion control treatment to prevent lead release from pipes and plumbing. Lead exposure can damage children's brains and nervous systems, lead to slow growth and development, and result in learning, behavior, hearing, and speech problems. After the involvement of concerned residents and independent researchers, Flint was reconnected to the Detroit water system on October 16, 2015. A federal emergency was declared in January 2016. PROGRAM: The Centers for Disease Control and Prevention provided assistance and support for response and recovery efforts including coordinating effective health messaging; assessing lead exposure; providing guidance on blood lead screening protocols; and identifying and linking community members to appropriate follow-up services.In response to the crisis in Flint, Congress funded the Centers for Disease Control and Prevention to establish a federal advisory committee; enhance Childhood Lead Poisoning Prevention Program activities; and support a voluntary Flint lead exposure registry. The registry, funded through a grant to Michigan State University, is designed to identify eligible participants and ensure robust registry data; monitor health, child development, service utilization, and ongoing lead exposure; improve service delivery to lead-exposed individuals; and coordinate with other community and federally funded programs in Flint. The registry is also collaborating to make Flint "lead-free" and to share best practices with other communities. DISCUSSION: The Flint water crisis highlights the need for improved risk communication strategies, and environmental health infrastructure, enhanced surveillance, and primary prevention to identify and respond to environmental threats to the public's health. Collecting data is important to facilitate action and decision making to prevent lead poisoning. Partnerships can help guide innovative strategies for primary lead prevention, raise awareness, extend outreach and communication efforts, and promote a shared sense of ownership. |
A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus.
Flint M , Chatterjee P , Lin DL , McMullan LK , Shrivastava-Ranjan P , Bergeron E , Lo MK , Welch SR , Nichol ST , Tai AW , Spiropoulou CF . Nat Commun 2019 10 (1) 285 There are no approved therapies for Ebola virus infection. Here, to find potential therapeutic targets, we perform a screen for genes essential for Ebola virus (EBOV) infection. We identify GNPTAB, which encodes the alpha and beta subunits of N-acetylglucosamine-1-phosphate transferase. We show that EBOV infection of a GNPTAB knockout cell line is impaired, and that this is reversed by reconstituting GNPTAB expression. Fibroblasts from patients with mucolipidosis II, a disorder associated with mutations in GNPTAB, are refractory to EBOV, whereas cells from their healthy parents support infection. Impaired infection correlates with loss of the expression of cathepsin B, known to be essential for EBOV entry. GNPTAB activity is dependent upon proteolytic cleavage by the SKI-1/S1P protease. Inhibiting this protease with the small-molecule PF-429242 blocks EBOV entry and infection. Disruption of GNPTAB function may represent a strategy for a host-targeted therapy for EBOV. |
Emergency preparedness is equally important as response in optimizing the health and well-being of the nation's children
Peacock G , So M , Franks J . Pediatrics 2018 142 (4) We commend the policy statement by Kuo et al1 in which they highlight the critical need for collaboration between pediatric and public health sectors in safeguarding the health of our nation’s children,1 and in particular, we commend the authors’ emphasis on emergency management and response efforts surrounding the 2016 Flint water contamination crisis, 2015 Zika virus emergency, and 2015 Disneyland measles outbreak. In addition, we agree that synergy between public health and pediatricians on emergency preparedness is a key opportunity for primary prevention and health promotion. In this letter, we highlight the crucial partnership between the American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC) and discuss ongoing preparedness activities used to address the call to action put forth by Kuo et al.1 |
Youth Risk Behavior Surveillance - United States, 2017
Kann L , McManus T , Harris WA , Shanklin SL , Flint KH , Queen B , Lowry R , Chyen D , Whittle L , Thornton J , Lim C , Bradford D , Yamakawa Y , Leon M , Brener N , Ethier KA . MMWR Surveill Summ 2018 67 (8) 1-114 PROBLEM: Health-risk behaviors contribute to the leading causes of morbidity and mortality among youth and adults in the United States. In addition, significant health disparities exist among demographic subgroups of youth defined by sex, race/ethnicity, and grade in school and between sexual minority and nonsexual minority youth. Population-based data on the most important health-related behaviors at the national, state, and local levels can be used to help monitor the effectiveness of public health interventions designed to protect and promote the health of youth at the national, state, and local levels. REPORTING PERIOD COVERED: September 2016-December 2017. DESCRIPTION OF THE SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-related behaviors among youth and young adults: 1) behaviors that contribute to unintentional injuries and violence; 2) tobacco use; 3) alcohol and other drug use; 4) sexual behaviors related to unintended pregnancy and sexually transmitted infections (STIs), including human immunodeficiency virus (HIV) infection; 5) unhealthy dietary behaviors; and 6) physical inactivity. In addition, YRBSS monitors the prevalence of other health-related behaviors, obesity, and asthma. YRBSS includes a national school-based Youth Risk Behavior Survey (YRBS) conducted by CDC and state and large urban school district school-based YRBSs conducted by state and local education and health agencies. Starting with the 2015 YRBSS cycle, a question to ascertain sexual identity and a question to ascertain sex of sexual contacts were added to the national YRBS questionnaire and to the standard YRBS questionnaire used by the states and large urban school districts as a starting point for their questionnaires. This report summarizes results from the 2017 national YRBS for 121 health-related behaviors and for obesity, overweight, and asthma by demographic subgroups defined by sex, race/ethnicity, and grade in school and by sexual minority status; updates the numbers of sexual minority students nationwide; and describes overall trends in health-related behaviors during 1991-2017. This reports also summarizes results from 39 state and 21 large urban school district surveys with weighted data for the 2017 YRBSS cycle by sex and sexual minority status (where available). RESULTS: Results from the 2017 national YRBS indicated that many high school students are engaged in health-risk behaviors associated with the leading causes of death among persons aged 10-24 years in the United States. During the 30 days before the survey, 39.2% of high school students nationwide (among the 62.8% who drove a car or other vehicle during the 30 days before the survey) had texted or e-mailed while driving, 29.8% reported current alcohol use, and 19.8% reported current marijuana use. In addition, 14.0% of students had taken prescription pain medicine without a doctor's prescription or differently than how a doctor told them to use it one or more times during their life. During the 12 months before the survey, 19.0% had been bullied on school property and 7.4% had attempted suicide. Many high school students are engaged in sexual risk behaviors that relate to unintended pregnancies and STIs, including HIV infection. Nationwide, 39.5% of students had ever had sexual intercourse and 9.7% had had sexual intercourse with four or more persons during their life. Among currently sexually active students, 53.8% reported that either they or their partner had used a condom during their last sexual intercourse. Results from the 2017 national YRBS also indicated many high school students are engaged in behaviors associated with chronic diseases, such as cardiovascular disease, cancer, and diabetes. Nationwide, 8.8% of high school students had smoked cigarettes and 13.2% had used an electronic vapor product on at least 1 day during the 30 days before the survey. Forty-three percent played video or computer games or used a computer for 3 or more hours per day on an average school day for something that was not school work and 15.4% had not been physically active for a total of at least 60 minutes on at least 1 day during the 7 days before the survey. Further, 14.8% had obesity and 15.6% were overweight. The prevalence of most health-related behaviors varies by sex, race/ethnicity, and, particularly, sexual identity and sex of sexual contacts. Specifically, the prevalence of many health-risk behaviors is significantly higher among sexual minority students compared with nonsexual minority students. Nonetheless, analysis of long-term temporal trends indicates that the overall prevalence of most health-risk behaviors has moved in the desired direction. INTERPRETATION: Most high school students cope with the transition from childhood through adolescence to adulthood successfully and become healthy and productive adults. However, this report documents that some subgroups of students defined by sex, race/ethnicity, grade in school, and especially sexual minority status have a higher prevalence of many health-risk behaviors that might place them at risk for unnecessary or premature mortality, morbidity, and social problems (e.g., academic failure, poverty, and crime). PUBLIC HEALTH ACTION: YRBSS data are used widely to compare the prevalence of health-related behaviors among subpopulations of students; assess trends in health-related behaviors over time; monitor progress toward achieving 21 national health objectives; provide comparable state and large urban school district data; and take public health actions to decrease health-risk behaviors and improve health outcomes among youth. Using this and other reports based on scientifically sound data is important for raising awareness about the prevalence of health-related behaviors among students in grades 9-12, especially sexual minority students, among decision makers, the public, and a wide variety of agencies and organizations that work with youth. These agencies and organizations, including schools and youth-friendly health care providers, can help facilitate access to critically important education, health care, and high-impact, evidence-based interventions. |
Statins suppress Ebola virus infectivity by interfering with glycoprotein processing
Shrivastava-Ranjan P , Flint M , Bergeron E , McElroy AK , Chatterjee P , Albarino CG , Nichol ST , Spiropoulou CF . mBio 2018 9 (3) Ebola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Statins, widely used cholesterol-lowering drugs, have pleiotropic mechanisms of action and were suggested as potential adjunct therapy for Ebola virus disease (EVD) during the 2013-2016 outbreak in West Africa. Here, we evaluated the antiviral effects of statin (lovastatin) on EBOV infection in vitro Statin treatment decreased infectious EBOV production in primary human monocyte-derived macrophages and in the hepatic cell line Huh7. Statin treatment did not interfere with viral entry, but the viral particles released from treated cells showed reduced infectivity due to inhibition of viral glycoprotein processing, as evidenced by decreased ratios of the mature glycoprotein form to precursor form. Statin-induced inhibition of infectious virus production and glycoprotein processing was reversed by exogenous mevalonate, the rate-limiting product of the cholesterol biosynthesis pathway, but not by low-density lipoprotein. Finally, statin-treated cells produced EBOV particles devoid of the surface glycoproteins required for virus infectivity. Our findings demonstrate that statin treatment inhibits EBOV infection and suggest that the efficacy of statin treatment should be evaluated in appropriate animal models of EVD.IMPORTANCE Treatments targeting Ebola virus disease (EVD) are experimental, expensive, and scarce. Statins are inexpensive generic drugs that have been used for many years for the treatment of hypercholesterolemia and have a favorable safety profile. Here, we show the antiviral effects of statins on infectious Ebola virus (EBOV) production. Our study reveals a novel molecular mechanism in which statin regulates EBOV particle infectivity by preventing glycoprotein processing and incorporation into virus particles. Additionally, statins have anti-inflammatory and immunomodulatory effects. Since inflammation and dysregulation of the immune system are characteristic features of EVD, statins could be explored as part of EVD therapeutics. |
Assessment of behavioral health concerns in the community affected by the Flint Water Crisis - Michigan (USA) 2016
Fortenberry GZ , Reynolds P , Burrer SL , Johnson-Lawrence V , Wang A , Schnall A , Pullins P , Kieszak S , Bayleyegn T , Wolkin A . Prehosp Disaster Med 2018 33 (3) 1-10 OBJECTIVES: The Flint Community Resilience Group (Flint, Michigan USA) and the Centers for Disease Control and Prevention (CDC; Atlanta, Georgia USA) assessed behavioral health concerns among community members to determine the impact of lead contamination of the Flint, Michigan water supply. METHODS: A Community Assessment for Public Health Emergency Response (CASPER) was conducted from May 17 through May 19, 2016 using a multi-stage cluster sampling design to select households and individuals to interview. RESULTS: One-half of households felt overlooked by decision makers. The majority of households self-reported that at least one member experienced more behavioral health concerns than usual. The prevalence of negative quality of life indicators and financial concerns in Flint was higher than previously reported in the Michigan 2012 and 2014 Behavioral Risk Factor Surveillance System (BRFSS) survey. CONCLUSIONS: The following can be considered to guide recovery efforts in Flint: identifying additional resources for behavioral health interventions and conducting follow-up behavioral health assessments to evaluate changes in behavioral health concerns over time; considering the impact of household economic factors when implementing behavioral health interventions; and ensuring community involvement and engagement in recovery efforts to ease community stress and anxiety. FortenberryGZ, ReynoldsP, BurrerSL, Johnson-LawrenceV, WangA, SchnallA, PullinsP, KieszakS, BayleyegnT, WolkinA. Assessment of behavioral health concerns in the community affected by the Flint water crisis - Michigan (USA) 2016. |
Lessons learnt from a three-year pilot field epidemiology training programme
Hoy D , Durand AM , Hancock T , Cash HL , Hardie K , Paterson B , Paulino Y , White P , Merritt T , Fitzgibbons D , Gopalani SV , Flint J , Edwin AMerilles O Jr , Kashiwabara M , Biaukula V , Lepers C , Souares Y , Nilles E , Batikawai A , Huseynova S , Patel M , Saketa ST , Durrheim D , Henderson A , Roth A . Western Pac Surveill Response J 2017 8 (3) 21-26 PROBLEM: The Pacific region has widely dispersed populations, limited financial and human resources and a high burden of disease. There is an urgent need to improve the availability, reliability and timeliness of useable health data. CONTEXT: The purpose of this paper is to share lessons learnt from a three-year pilot field epidemiology training programme that was designed to respond to these Pacific health challenges. The pilot programme built on and further developed an existing field epidemiology training programme for Pacific health staff. ACTION: The programme was delivered in country by epidemiologists working for Pacific Public Health Surveillance Network partners. The programme consisted of five courses: four one-week classroom-based courses and one field epidemiology project. Sessions were structured so that theoretical understanding was achieved through interaction and reinforced through practical hands-on group activities, case studies and other interactive practical learning methods. OUTCOME: As of September 2016, 258 students had commenced the programme. Twenty-six course workshops were delivered and one cohort of students had completed the full five-course programme. The programme proved popular and gained a high level of student engagement. DISCUSSION: Face-to-face delivery, a low student-to-facilitator ratio, substantial group work and practical exercises were identified as key factors that contributed to the students developing skills and confidence. Close engagement of leaders and the need to quickly evaluate and adapt the curriculum were important lessons, and the collaboration between external partners was considered important for promoting a harmonized approach to health needs in the Pacific. |
Identification of 2'-deoxy-2'-fluorocytidine as a potent inhibitor of Crimean-Congo hemorrhagic fever virus replication using a recombinant fluorescent reporter virus
Welch SR , Scholte FEM , Flint M , Chatterjee P , Nichol ST , Bergeron E , Spiropoulou CF . Antiviral Res 2017 147 91-99 Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne orthonairovirus, causes a severe hemorrhagic disease in humans (Crimean-Congo hemorrhagic fever, CCHF). Currently, no vaccines are approved to prevent CCHF; treatment is limited to supportive care and the use of ribavirin, the therapeutic benefits of which remain unclear. CCHF is part of WHO's priority list of infectious diseases warranting further research and development. To aid in the identification of new antiviral compounds, we generated a recombinant CCHFV expressing a reporter protein, allowing us to quantify virus inhibition by measuring the reduction in fluorescence in infected cells treated with candidate compounds. The screening assay was readily adaptable to high-throughput screening (HTS) of compounds using Huh7 cells, with a signal-to-noise ratio of 50:1, and Z'-factors > 0.6 in both 96- and 384-well formats. A screen of candidate nucleoside analog compounds identified 2'-deoxy-2'-fluorocytidine (EC50 = 61 +/- 18 nM) as having 200 x the potency of ribavirin (EC50 = 12.5 +/- 2.6 muM), as well as 17 x the potency of T-705 (favipiravir), another compound with reported anti-CCHFV activity (EC50 = 1.03 +/- 0.16 muM). Furthermore, we also determined that 2'-deoxy-2'-fluorocytidine acts synergistically with T-705 to inhibit CCHFV replication without causing cytotoxicity. The incorporation of this reporter virus into the high-throughput screening assay described here will allow more rapid identification of effective therapeutic options to combat this emerging human pathogen. |
Flex-nucleoside analogues - Novel therapeutics against filoviruses
Yates MK , Raje MR , Chatterjee P , Spiropoulou CF , Bavari S , Flint M , Soloveva V , Seley-Radtke KL . Bioorg Med Chem Lett 2017 27 (12) 2800-2802 Fleximers, a novel type of flexible nucleoside that have garnered attention due to their unprecedented activity against human coronaviruses, have now exhibited highly promising levels of activity against filoviruses. The Flex-nucleoside was the most potent against recombinant Ebola virus in Huh7 cells with an EC50=2muM, while the McGuigan prodrug was most active against Sudan virus-infected HeLa cells with an EC50 of 7muM. |
GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses
Lo MK , Jordan R , Arvey A , Sudhamsu J , Shrivastava-Ranjan P , Hotard AL , Flint M , McMullan LK , Siegel D , Clarke MO , Mackman RL , Hui HC , Perron M , Ray AS , Cihlar T , Nichol ST , Spiropoulou CF . Sci Rep 2017 7 43395 GS-5734 is a monophosphate prodrug of an adenosine nucleoside analog that showed therapeutic efficacy in a non-human primate model of Ebola virus infection. It has been administered under compassionate use to two Ebola patients, both of whom survived, and is currently in Phase 2 clinical development for treatment of Ebola virus disease. Here we report the antiviral activities of GS-5734 and the parent nucleoside analog across multiple virus families, providing evidence to support new indications for this compound against human viruses of significant public health concern. |
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